MAD2 is a mitotic checkpoint gene whose function is required for yeast cells to arrest before undergoing cell division if the mitotic spindle apparatus is improperly attached to the chromosomes. (Li and Murray). In the absence of functional MAD2 protein, yeast cells which are exposed to drugs which inhibit the formation of a mitotic spindle, such as benomyl, vinblastine, nocodozole, etc. undergo rapid cell death due to massive chromosome loss. Yeast cells which have a functional MAD2 protein can survive such drug treatment because they are able to stop dividing prior to the chromosome loss event.
The interest in the MAD2 gene stems from the possibility that tumor cells that are hypersensitive to chemotherapeutic agents which inhibit the formation of the mitotic spindle may be sensitive to these drugs precisely because they are defective in the MAD2 checkpoint. Analysis of the MAD2 status of a given tumor may therefore be a predictor of chemosensitivity. In addition, the loss of MAD2 function in a normal cell may predispose that cell to aberrant chromosome segregation events, a hallmark of tumor progression.